We have found that urinary extracts (CH2Cl2) of man on high NaCl intake produce net Cl- outflux (active Cl- transport) in isolated short-circuited frog skin. Activity is not found in urine of NaCl deprived normal or NaCl loaded adrenal insufficient subjects. Our findings indicate that the factor is of adrenal origin and that it induces active ion transport in the direction opposite to that stimulated by the adrenal hormone aldosterone. Aldosterone produces NaCl conservation in states of salt deprivation. We expect this factor to produce NaCl excretion in states of excess salt ingestion. Indeed recent Ns ion flux studies show Na ion outflux increase concomitant with Cl- transport changes indicating that the factor induces both Na ion and Cl- secretion. Initial purification studies demonstrate factor activity in a fraction of intermediate polarity on Sephadex LH20 chromatography. Also, the activity in urine is enhanced by glucuronidase - sulfatase hydrolysis. Our first and major aim is purification, isolaton, identification and development of a specific assay for the factor. Sephadex column chromatography, high pressure liquid chromatography, gas liquid chromatography and combined GLC/mass spectroscopy will be utilized. Our long range goals are: 1) to determine the effects of the factor in mammalian renal and intestinal systems, when sufficient quantities of the pure material are available; 2) assess factors which regulate its release in man; 3) evaluate its role in ECF volume regulation in health and in certain disease states in man; and 4) perform more detailed studies of its cellular mode of action in epithelia.